Phytomedicine最新文献

{"title":"The effectiveness and safety of Chinese herbal Jieyu Anshen Decoction monotherapy or in combination with Western medicine for mental disorders: A systematic review and meta-analysis of randomized controlled trials.","authors":"Kai Liu, Ze-Yang Shi, Yi-Ke Song, Jian-Li Wang, Hong-Zhan Jiang, Xian Zhou, Jiang-Hong Liu, Jian-Ping Liu, Zhao-Lan Liu","doi":"10.1016/j.phymed.2025.157351","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157351","url":null,"abstract":"<p><strong>Background: </strong>Mental disorders are a major global health challenge. While Western medicine (WM) is the primary treatment, its limitations create a need for complementary and alternative therapies.</p><p><strong>Objective: </strong>Evaluate the effectiveness and safety of Chinese herbal medicine Jieyu Anshen Decoction (JYASD) in treating mental disorders, both as monotherapy and in combination with WM.</p><p><strong>Methods: </strong>Eight databases were searched from their inception to October 2024. Randomized controlled trials (RCTs) on JYASD for mental disorders were included. Meta-analysis was performed, and Risk of bias and evidence quality were assessed.</p><p><strong>Results: </strong>A total of 95 RCTs involving 8188 participants were included, comparing JYASD with 23 types of WM across four categories of mental disorders. For adjuvant therapy, JYASD combined with paroxetine showed superior effectiveness in treating depressive disorder (RR = 1.18, 95 % CI: 1.13-1.23) and anxiety disorders (RR = 1.30, 95 % CI: 1.17-1.44), with significant improvements in HAMD and HAMA scores compared with WM monotherapy. For schizophrenia, JYASD combined with aripiprazole showed positive effects compared with WM monotherapy (RR = 1.21, 95 % CI: 1.11-1.31). For monotherapy, JYASD was as effective as paroxetine and more than fluoxetine for depressive disorder, while showing significant advantage over estazolam for sleep disorders (RR = 1.15, 95 % CI: 1.07-1.23). Both adjuvant therapy and JYASD alone had significantly fewer adverse events than WM alone, especially with paroxetine (RR = 0.13, 95 % CI: 0.05-0.33).</p><p><strong>Conclusion: </strong>JYASD shows promising therapeutic value in treating mental disorders, both as monotherapy and adjuvant therapy, with favorable safety profiles and stable therapeutic effects.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157351"},"PeriodicalIF":8.3,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin ameliorates doxorubicin-induced atrial fibrillation via EGFR-mediated restoration of autophagic flux.","authors":"Wei-Hua Bian, Shi-Hao Wang, Ze-Chun Kang, Yong Xu, Ya-Nuo Li, Mei-Zi Yang, Jun-Hou Yang, Jun-Yao Liu, Yan-Li Cheng, Dong Chang, Xin Xie","doi":"10.1016/j.phymed.2025.157357","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157357","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is a widely used chemotherapeutic agent associated with significant cardiotoxicity, particularly manifesting as atrial fibrillation (AF), which adversely impacts patient quality of life.</p><p><strong>Purpose: </strong>This study aimed to investigate the effects of quercetin and its underlying mechanisms in doxorubicin (DOX)-induced AF.</p><p><strong>Methods: </strong>Utilizing a mouse model, we compared DOX treatment with quercetin pre-treatment, examining the incidence and duration of AF, as well as the associated structural alterations in the atria, encompassing atrial enlargement, fibrotic changes, and oxidative stress.</p><p><strong>Results: </strong>The findings from our study indicated that quercetin significantly alleviated DOX-induced AF by inhibiting phosphorylation of EGFR and TFEB, which consequently inhibited ATG5-mediated autophagosome formation and enhanced lysosomal degradation. Moreover, the use of an EGFR phosphorylation inhibitor, Nsc228155, reversed these effects at both cellular and murine levels. Furthermore, Knockdown of ATG5 by rAVV9-shATG5 strengthened the protective effects of quercetin on DOX-induce AF, whereas cardiac-specific overexpression of ATG5 by rAVV9-ATG5 partially abolished the protective effects of quercetin.</p><p><strong>Conclusion: </strong>This work firstly reveals that quercetin prevents DOX-induced AF by targeting a novel EGFR/TFEB/ATG5-mediated autophagy-lysosomal axis, establishing it as the inaugural natural compound antagonizing chemotherapy-induced arrhythmia via phospho-EGFR inhibition. Our findings pioneer a therapeutic paradigm shifting from conventional antioxidant strategies toward precision autophagy modulation, offering highly translatable cardioprotection for cancer patients with immediate clinical potential.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157357"},"PeriodicalIF":8.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shen-Bai-Jie-Du decoction inhibits colorectal tumorigenesis by attenuating the malignancy of cancer stem cells via the gut microbiota-bile acid-FXR axis.","authors":"Ye Zhang, Meng Shen, Jianaer Baokan, Liting Xu, Mingxin Ni, Junyan Jin, Weixing Shen, Dongdong Sun, Liu Li, Yueyang Lai, Qiuying Yan, Chengtao Yu, Jiani Tan, Changliang Xu, Lihuiping Tao, Minmin Fan, Haibo Cheng","doi":"10.1016/j.phymed.2025.157366","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157366","url":null,"abstract":"<p><strong>Background: </strong>Shen-Bai-Jie-Du decoction (SBJDD), a traditional Chinese herbal formula grounded in evidence-based medicine, demonstrates efficacy in reducing the recurrence and carcinogenesis of colorectal adenoma (CRA). However, the mechanism by which SBJDD inhibits CRA carcinogenesis remains unclear.</p><p><strong>Purpose: </strong>This study aimed to elucidate the mechanism through which SBJDD suppresses colorectal cancer stem cell (CSC) aggressiveness by modulating the gut microbiota-bile acid (BA)-Farnesoid X receptor (FXR) signaling axis.</p><p><strong>Methods: </strong>The APC^min/+ mouse model and subcutaneously tumor-bearing mouse model were established to investigate the efficacy and underlying mechanisms of SBJDD in CRA carcinogenesis. Multi-omics analyses were conducted using 16S rRNA, metabolomics, and transcriptome sequencing. The pharmacological effects and mechanisms of SBJDD were evaluated through RT-qPCR, immunohistochemical staining, molecular docking, Western blot, immunofluorescence staining, and flow cytometry assay. Moreover, paired fecal samples and adenoma tissues were collected from CRA patients to further validate the findings.</p><p><strong>Results: </strong>Our findings demonstrated that SBJDD can protect the integrity of the intestinal mucosal barrier, thereby inhibiting colorectal tumorigenesis. Mechanistically, our study revealed that SBJDD can reduce the fecal abundance of BA-producing gut microbiota. Meanwhile, we confirmed that the BA receptor FXR and its downstream target genes were significantly upregulated following SBJDD administration, and molecular docking analyses demonstrated that the bioactive components of SBJDD can bind to FXR. Moreover, we showed that SBJDD can downregulate CSC marker genes by regulating FXR signaling pathways.</p><p><strong>Conclusion: </strong>Our study objectively verified that SBJDD can alleviate the malignancy of CSCs by modulating the gut microbiota-bile acid-FXR axis, ultimately suppressing the progression from colorectal adenoma to carcinoma.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157366"},"PeriodicalIF":8.3,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yuzhuo Zhixiao pill can treat non-alcoholic steatohepatitis through modulation of gut microbiota, bile acid and short-chain fatty acid metabolism","authors":"Yuanqin Du ,&nbsp;Jian Xu ,&nbsp;Juhong Jia ,&nbsp;Yaobin Nong ,&nbsp;Yong Lin ,&nbsp;Yixian Ye ,&nbsp;Yuexue Zhong ,&nbsp;Qinwen Tan ,&nbsp;Yanfei Wei ,&nbsp;Guihua Huang ,&nbsp;Dewen Mao ,&nbsp;Guochu Huang ,&nbsp;Lu Lu ,&nbsp;Yujiao Peng ,&nbsp;Hongna Huang ,&nbsp;Jingjing Huang","doi":"10.1016/j.phymed.2025.157348","DOIUrl":"10.1016/j.phymed.2025.157348","url":null,"abstract":"<div><h3>Background</h3><div>Yuzhuo Zhixiao Pill (YZZXP), a formulation in traditional Chinese medicine (TCM), exhibits therapeutic potential in non-alcoholic steatohepatitis (NASH). However, the mechanisms underlying its effects, particularly those involving gut microbiota–bile acid–short-chain fatty acid (GM–BA–SCFA) interactions, remain unclear. Current therapies present notable side effects and inadequately address the multifactorial etiology of NASH.</div></div><div><h3>Purpose</h3><div>To evaluate the anti-NASH efficacy of YZZXP and elucidate its mechanism, focusing on GM remodeling and BA/SCFA regulation.</div></div><div><h3>Study design</h3><div>This study established a NASH model in rats using a high-fat diet (HFD) and performed fecal microbiota transplantation (FMT) experiments.</div></div><div><h3>Methods</h3><div>The therapeutic impacts of YZZXP on gut microbial structure (16S rDNA sequencing), SCFA concentrations, and BA profiles (analyzed by LC-MS and GC-MS) were assessed.</div></div><div><h3>Results</h3><div>YZZXP administration alleviated HFD-induced obesity, hepatic steatosis, inflammatory responses, and disturbances in glycolipid metabolism. Microbial profiling via 16S rDNA sequencing revealed restored gut microbial diversity, marked by increased <em>Akkermansia, Bacteroides</em>, and <em>Roseburia</em> abundance. PROB and FMT interventions validated GM modulation as central to YZZXP 's effects. Targeted metabolomic analyses demonstrated elevated levels of SCFAs (notably butyrate and acetate) and substantial shifts in BA composition, accompanied by downregulation of intestinal FXR-FGF19 signaling and enhanced cholesterol excretion.</div></div><div><h3>Conclusions</h3><div>YZZXP exerts anti-NASH activity through a synergistic mechanism comprising GM restoration, BA metabolic reprogramming via FXR pathway inhibition, and SCFA-driven metabolic modulation. In contrast to monotherapy approaches, the multi-target strategy of YZZXP prevents compensatory dysbiosis and yields more durable metabolic benefits than PROB or FMT alone. By integrating microbiota-metabolite interplay into therapeutic design, YZZXP introduces a novel paradigm in traditional medicine for NASH management, addressing the limitations of synthetic agents while promoting metabolic homeostasis.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157348"},"PeriodicalIF":8.3,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Royal jelly acid inhibits NF-κB signaling by regulating H3 histone lactylation to alleviate IgE-mediated mast cell activation and allergic inflammation","authors":"Xue-Ting Xu ,&nbsp;Jun-Kai Fan ,&nbsp;Xi Chen,&nbsp;Si-Yi Que,&nbsp;Run-Xin Zhang,&nbsp;Yu-Yan Xie,&nbsp;Tian-Ci Zhou,&nbsp;Kunmei Ji,&nbsp;Zhen-Fu Zhao,&nbsp;Jia-Jie Chen","doi":"10.1016/j.phymed.2025.157344","DOIUrl":"10.1016/j.phymed.2025.157344","url":null,"abstract":"<div><h3>Background</h3><div>Mast cells (MCs) mediate high-affinity IgE Fc receptor (FcεRI)-mediated allergic reactions. Royal jelly acid (RJA), the major lipid constituent of royal jelly, has anti-inflammatory, anti-tumor, antibacterial, and immunomodulatory properties.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate how RJA affects IgE-mediated MC activation and to elucidate mechanisms underlying anti-allergic effects.</div></div><div><h3>Methods</h3><div>Mouse bone marrow-derived mast cells (BMMCs) and rat basophilic leukemia cells-2H3 (RBLs) were stimulated with IgE-antigen (Ag). β-hexosaminidase (β‑hex) and histamine (HA) release, inflammatory cytokines expression, and cellular morphology changes were examined in stimulated cells. Transcriptome changes associated with RJA-treated activated-MCs were analyzed. Network pharmacology, gene expression, and western blot analyses were employed to explore the relationship between H3 lactylation and anti-allergic effects of RJA on MC. In vivo studies were conducted in IgE-mediated passive cutaneous anaphylaxis (PCA), ovalbumin (OVA)-induced active systemic anaphylaxis (ASA), and HA-induced passive systemic anaphylaxis (PSA) mouse models.</div></div><div><h3>Results</h3><div>RJA inhibited IgE-dependent MC activation as evidenced by reduced β‑hex and HA release. RJA inhibited MAPK and NF-κB signaling, down-regulated <em>RELA</em> and <em>NFκB1</em> transcripts, and decreased NF-κB reporter activity. RJA inhibited cellular H3 lactylation and H3K9 lactylation (H3K9la), leading to reduced histone lactyllysine enrichment in <em>RELA</em> or <em>NFκB1</em> promoter loci. RJA alleviated allergic symptoms in PCA and ASA mice by intraperitoneal injection or oral administration, but did not affect HA-induced hypothermia.</div></div><div><h3>Conclusion</h3><div>RJA inhibits IgE-dependent MC activation by reducing cellular H3K9la and suppressing NF-κB signaling via reduced histone lactyllysine enrichment in <em>RELA</em> or <em>NFκB1</em> promoter sites. RJA may support MC inhibition in the prevention and treatment of allergic diseases.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157344"},"PeriodicalIF":8.3,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of xanthohumol in senile osteoporosis: mTOR-driven regulation of AKT/mTOR/p70S6K autophagy axis in D-galactose models.","authors":"Tian-Shuang Xia, Sheng-Yan Xu, Yi-Ping Jiang, Kun Li, Rui-Qing Zhu, Ting Han, Hai-Liang Xin","doi":"10.1016/j.phymed.2025.157346","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157346","url":null,"abstract":"<p><strong>Background: </strong>Senile osteoporosis (SOP) is a bone disorder characterized by bone loss, structural deterioration, and increased fracture risk. Xanthohumol (XAN), a bioactive isoflavone derived from Humulus lupulus L., shows potential bone-protective properties.</p><p><strong>Purpose: </strong>This study aimed to evaluate the anti-SOP efficacy of XAN and clarify its mechanisms through multidisciplinary approaches.</p><p><strong>Methods: </strong>A SOP mouse model was established using d-galactose (D-gal), followed by a 12-week XAN treatment. Animal procedures were approved by the Ethics Committee of Naval Military Medical University (No. 202130301). Pharmacological evaluations were conducted using the Morris water maze and Micro-CT. Mechanisms were predicted through integrated transcriptome analysis and metabolomics. In vitro, a d-gal-induced SOP model was established in MC3T3-E1 osteoblasts. The autophagy inhibitor 3-methyladenine (3-MA) or beclin-1 siRNA was applied to evaluate the effect of XAN on osteoblast function. Target identification was performed using drug affinity responsive target stability (DARTS), molecular docking, molecular dynamics, cellular thermal shift assay (CETSA), and microscale thermophoresis (MST) to assess the targeting action of XAN.</p><p><strong>Results: </strong>XAN improved bone quality and cognitive function in aging mice, demonstrating its potent anti-SOP effects. Metabolomics and femur immunohistochemistry indicated that XAN mitigated bone loss primarily by AKT/mTOR/p70S6K activation. In vitro, XAN enhanced cell differentiation, promoted mineralized nodule formation, and reduced apoptosis and senescence in d-gal-injured osteoblasts. These cytoprotective effects were counteracted by autophagy inhibition with 3-MA or beclin-1 siRNA. Moreover, XAN promoted autophagosome flux toward autolysosome, up-regulated beclin-1, and down-regulated key proteins in the AKT/mTOR/p70S6K pathway. Importantly, binding assays identified mTOR as a direct target of XAN, which was further validated in vivo using the mTOR-specific agonist MHY1485 and inhibitor rapamycin.</p><p><strong>Conclusions: </strong>Our study innovatively reveals that XAN prevents age-related bone loss by targeting mTOR and regulating the AKT/mTOR/p70S6K autophagy axis. This work provides the first mechanistic evidence supporting the potential of XAN as a natural therapeutic agent for SOP.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157346"},"PeriodicalIF":8.3,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemicals as modulators of Astrocytes in Alzheimer's disease: A therapeutic perspective.","authors":"Shaojun Wang, Zhigang Zhang, Yilin Liu, Songlan Gao, Lin Wang, Jun Yang, Yu Wang","doi":"10.1016/j.phymed.2025.157347","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157347","url":null,"abstract":"<p><strong>Background: </strong>Astrocytes play a crucial role in Alzheimer's disease (AD) pathogenesis, contributing to inflammation, amyloid plaque formation, and disease progression, making them promising therapeutic targets. Despite extensive research, the mechanisms underlying astrocytic dysfunction in AD and their modulation by phytochemicals remain incompletely understood, representing a critical gap in current knowledge.</p><p><strong>Purpose: </strong>This review aims to elucidate the pathological mechanisms involving astrocytes in AD and evaluate the therapeutic potential of phytochemicals in modulating astrocytic activity.</p><p><strong>Methods: </strong>We systematically analysed recent studies on astrocytic activation, target receptors, and signalling pathways in AD and their regulation by phytochemicals. The studies were identified through searches of databases including PubMed, Web of Science, ScienceDirect, and Google Scholar.</p><p><strong>Results: </strong>Our findings reveal that abnormal activation of astrocytic receptors and downstream signaling pathways, such as RAGE/NF-κB, ERK/c-fos/NFATc1, AKT/Nrf2/NF-κB, and PI3K/Akt/GSK-3β, disrupt immune homeostasis in AD models. Phytochemicals, including tanshinone IIA, honokiol, aucubin, cornuside, luteolin, naringenin, daphnetin, and gelsemine, show promising effects in delaying AD progression. These effects are mediated through multiple mechanisms, such as inhibiting pro-inflammatory pathways, enhancing anti-inflammatory responses, promoting Aβ clearance, stimulating synaptogenesis, regulating neurotrophic factors, and reducing oxidative stress. These findings highlight the pivotal role of astrocytes in AD pathophysiology and the potential of phytochemicals to modulate astrocytic dysfunction.</p><p><strong>Conclusions: </strong>By providing a comprehensive overview of astrocytic mechanisms and therapeutic interventions, this review offers a theoretical foundation for developing phytochemical-based strategies in AD therapy and underscores the need for further preclinical and clinical investigations to translate these findings into practical treatments.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157347"},"PeriodicalIF":8.3,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juglone promotes spinal cord injury recovery by suppressing pyroptosis and necroptosis through FOS/USP53/ubiquitination","authors":"Lu Chen ,&nbsp;Yong Chang ,&nbsp;Shiji Zhang ,&nbsp;Zihang Wang ,&nbsp;Haoran Liu ,&nbsp;Hongliang Wang ,&nbsp;Lusen Shi ,&nbsp;Na Li ,&nbsp;Shiqing Feng","doi":"10.1016/j.phymed.2025.157341","DOIUrl":"10.1016/j.phymed.2025.157341","url":null,"abstract":"<div><h3>Background</h3><div>Spinal cord injury (SCI) is a central nervous system (CNS) disorder, and it often results in severe neuronal damage. However, there are still no effective treatments for SCI, so it is important to explore and identify effective therapeutic strategies. As a natural compound extracted from walnuts, juglone has been previously reported to exhibit various biological activities, including anti-tumor and anti-inflammatory effects, but the effects on central nerve system are still blank.</div></div><div><h3>Purpose</h3><div>This study aims to evaluate the therapeutic effects of juglone in spinal cord injury and elucidate its molecular mechanisms in neuroprotection.</div></div><div><h3>Study design</h3><div>In vitro neuronal OGD/R experiments and in vivo spinal cord injury model experiments were employed to investigate the neuroprotective effects of juglone on neurons.</div></div><div><h3>Methods</h3><div>Neuronal OGD/R models and spinal cord injury models were used to detect the neuroprotective effect of juglone. Immunofluorescence, Western Blot and ELISA were employed to investigate the effects of juglone on necroptosis and pyroptosis of neurons. RNA-Seq analysis, immunoprecipitation, Western Blot, qRT-PCR, immunofluorescence and ChIP-qPCR were utilized to elucidate the molecular mechanism of its neuroprotective effect.</div></div><div><h3>Results</h3><div>Juglone can inhibit necroptosis and pyroptosis both in vivo and in vitro, thereby exerting neuroprotective effects. Mechanistically, we identify a novel FOS/USP53 signaling axis, in which juglone suppresses the expression of FOS that directly regulates the deubiquitinating enzyme USP53. Reduced FOS expression leads to the downregulation of USP53, thereby promoting the ubiquitination and degradation of MLKL and GSDMD. This cascade ultimately alleviates necroptosis and pyroptosis in injured neurons.</div></div><div><h3>Conclusion</h3><div>Juglone is a potential neuroprotective drug that exerts its effect by inhibiting necroptosis and pyroptosis through the FOS/USP53/ubiquitination signaling axis. These findings provide a novel potential drug target for the treatment of spinal cord injury.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"Article 157341"},"PeriodicalIF":8.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145226985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated bioinformatics and large-scale clinical urine proteomics reveal Huangkui Capsules extract alleviating diabetic kidney disease.","authors":"Houfa Geng, Yiting Zhang, Fan Li, Wei Wang, Xiu Zang, Mengwen Wang, Ran Liu, Xuekui Liu, Qianqian Ning, Mengzhe Guo, Jun Liang","doi":"10.1016/j.phymed.2025.157337","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157337","url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes mellitus. As a clinical therapeutic drug for DKD, the treatment mechanism of Huangkui Capsules (HKC) has not been clarified, which affects its individualized medication for patients. The multi-target characteristics of traditional Chinese medicine make its mechanism research rather difficult.</p><p><strong>Purpose: </strong>This study adopted the research method of combining network pharmacology with proteomics to accurately explore the potential protein targets of HKC in treatment of DKD. Moreover, a large-scale prospective clinical trial was utilized to conduct urine proteome detection on DKD patients before and after HKC treatment, further verifying the protein targets of HKC in treatment of DKD and discovering protein markers that characterize the therapeutic effect.</p><p><strong>Methods: </strong>Firstly, the active ingredients of HKC were extracted with 70 % ethanol and analyzed by mass spectrometry. Meanwhile, the drug-containing serum of HKC was also analyzed by mass spectrometry to verify the active ingredients and their metabolites in the blood. By comparing the protein content changes of high-glucose-stimulated HEK293T cells before and after HKC administration, the potential targets of HKC in treating DKD were explored in combination with network pharmacology. At the same time, A prospective clinical trial was designed to recruit 80 DKD patients, who received standard hypoglycemic treatment and oral administration of HKC for 6 months. The urine proteomics of these patients was used to further verify these targets and search for protein markers reflecting the treatment.</p><p><strong>Results: </strong>There were 22 major active compounds in HKC extract, in which quercetin and palmitic acid are the main components, and the metabolites of these two main components were also found in the drug-containing serum of HKC. According to the cellular experiments, the extracellular matrix accumulation phenomenon of HEK293T cells stimulated by high glucose was alleviated after HKC administration. The proteins that were upregulated under high glucose stimulation and downregulated after HKC administration were selected and combined with network pharmacology analysis. Then a total of 4 known targets and 86 potential unknown targets of HKC were identified. Furthermore, we verified the above targets using the urine proteomics of DKD patients before and after HKC treatment. And combined with molecular docking, we found that quercetin and palmitic acid in HKC could improve renal injury in DKD patients through VEGF-A through RAP1 signaling and tight junction pathways.</p><p><strong>Conclusion: </strong>This study provides an integrated bioinformatics combined with large-scale clinical urine proteomics to verified the protein targets of HKC in the treatment of DKD.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157337"},"PeriodicalIF":8.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of natural polysaccharides in female-prevalent cancers.","authors":"Hao Li, Meiqi Jiang, Yaqing Fan, Yian Shen, Yuelong Han, Huijuan Xu, Biao Cai, Maowen Chen","doi":"10.1016/j.phymed.2025.157340","DOIUrl":"https://doi.org/10.1016/j.phymed.2025.157340","url":null,"abstract":"<p><strong>Background: </strong>Cancer remains a critical global health threat, significantly compromising women's health and survival rates worldwide. However, most current chemotherapy drugs are often limited in clinical application due to their substantial side effects. Therefore, there is a pressing demand for the discovery and development of novel drugs. Given their low toxicity and multifaceted bioactivities, natural polysaccharides have emerged as promising anticancer candidates, attracting considerable research attention for their therapeutic potential.</p><p><strong>Purpose: </strong>This comprehensive review synthesized the anti-tumor effects and underlying mechanisms of various polysaccharides. This review aims to consolidate fragmented evidence and bridge existing knowledge gaps, while providing a scientific basis for the clinical utility of bioactive polysaccharides in treating common female-specific tumors.</p><p><strong>Methods: </strong>A systematic literature search was conducted in Web of Science, PubMed, ScienceDirect, and ProQuest, as well as publisher databases (Elsevier, ACS, RSC, Springer) up to April 2025 using predefined keywords.</p><p><strong>Results: </strong>This study reviewed 179 articles published between 2010 and 2025, covering 81 polysaccharides obtained from 75 natural products. Among these publications, 48 were based on in vivo studies and 99 on in vitro studies. The molecular weight of the polysaccharides was reported in 25 articles, while monosaccharide composition was analyzed in 36 articles. Systematic analysis revealed that these polysaccharides exert therapeutic effects on common female cancers through multiple mechanisms, including inhibiting tumor cell proliferation and metastasis, inducing apoptosis, arresting cell cycle progression, enhancing immune surveillance, and modulating gut microbiota. Key signaling pathways involved include PI3K/AKT/mTOR, NF-κB, TNF-α, and MAPK, among others.</p><p><strong>Conclusion: </strong>The review highlights the potential of natural polysaccharides as anticancer resources, because they can modulate key cellular signaling pathways, which are critical for advancing targeted therapies against common tumors in women. Elucidating these antitumor mechanisms not only reveals therapeutic potentials but also facilitates innovative treatment strategies.</p>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"148 ","pages":"157340"},"PeriodicalIF":8.3,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145245015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}